Isolation, structural characterization, and bioactivity of a novel neuromedin U analog from the defensive skin secretion of the Australasian tree frog, Litoria caerulea

We report the isolation of a novel bioactive peptide, neuromedin U-23 (NmU- 23), from the defensive skin secretion of the Australasian tree frog, Litor ia caerulea. The primary structure of the peptide was established by a comb ination of microsequencing, mass spectroscopy and site-directed antiserum i mmunoreactivity as SDEEVQVPGGVISNGYFLFRPRN-amide (M-r 2580.6), A synthetic replicate of frog NmU-23 displaced monoradioiodinated rat NmU-23 from uteri ne membranes in a dose-dependent fashion indistinguishable from nonisotopic ally labeled rat NmU-23. In a rat uterine smooth muscle strip preparation, synthetic frog NmU-23 produced dose-dependent contractions identical to por cine NmU-25, However, in a preparation of human urinary bladder muscle stri p, the synthetic frog peptide was more potent than porcine NmU-25 in elicit ing contraction and produced desensitization of the preparation to the latt er peptide. This report demonstrates that the defensive skin secretion of a frog contains a novel peptide exhibiting a high degree of primary structur al similarity to the endogenous vertebrate peptide, NmU, and that this frog skin analog displays biological activity in mammalian tissues.